Three new coumarins and a new coumarin glycoside from Micromelum integerrimum / 中国天然药物

Three new coumarins, integmarins A-C (1-3), and a new coumarin glycoside, integmaside A (4) were isolated from the leaves and stems of Micromelum integerrimum. Their structures were elucidated on the basis of 1D and 2D NMR and MS data, and their absolute configurations were assigned according to the ECD data of the in situ formed transition metal complexes and comparison of experimental and calculated ECD data. Compounds 1 and 2 are two rare coumarins with butyl and propyl moieties at the C-6 position; compound 3 is a novel coumarin with a highly oxidized prenyl group, and compound 4 is a rare bisdihydrofuranocoumarin glycoside.

A new coumarin derivative, 4-acetatecoumarin, with antifungal activity and association study against Aspergillus spp

Abstract Fungal infections have become a concern for health professionals, and the emergence of resistant strains has been reported for all known classes of antifungal drugs. Among the fungi causing disease, we highlight those that belong to the genus Aspergillus. For these reasons, the search for new antifungals is important. This study examines the effects of a coumarin derivative, 4-acetatecoumarin (Cou-UMB16) both alone and together with antifungal drugs, and its mode of action against Aspergillus spp. Cou-UMB16 was tested to evaluate its effects on mycelia growth, and germination of Aspergillus spp. fungal conidia. We investigated its possible action on cell walls, on the cell membrane, and also the capacity of this coumarin derivative to enhance the activity of antifungal drugs. Our results suggest that Cou-UMB16 inhibits Aspergillus spp. virulence factors (mycelia growth and germination of conidia) and affects the structure of the fungal cell wall. When applying Cou-UMB16 in combination with azoles, both synergistic and additive effects were observed. This study concludes that Cou-UMB16 inhibits mycelial growth and spore germination, and that the activity is due to its action on the fungal cell wall, and that Cou-UMB16 could act as an antifungal modifier.

Leishmanicidal and cholinesterase inhibiting activities of phenolic compounds of Dimorphandra gardneriana and Platymiscium floribundum, native plants from Caatinga biome / Atividade inibitória Leishmanicida e Colinesterásica de Compostos Fenólicos de Dimorphandra gardneriana e Platymiscium fliribunbum, plantas nativas do bioma Caatinga

In recent years, the Brazilian Health Ministry and the World Health Organization have supported research into new technologies that may contribute to the surveillance, new treatments, and control of visceral leishmaniasis within the country. In light of this, the aim of this study was to isolate compounds from plants of the Caatinga biome, and to investigate their toxicity against promastigote and amastigote forms of Leishmania infantum chagasi, the main responsible parasite for South American visceral leishmaniasis, and evaluate their ability to inhibit acetylcholinesterase enzyme (AChE). A screen assay using luciferase-expressing promastigote form and an in situ ELISA assay were used to measure the viability of promastigote and amastigote forms, respectively, after exposure to these substances. The MTT colorimetric assay was performed to determine the toxicity of these compounds in murine monocytic RAW 264.7 cell line. All compounds were tested in vitro for their anti-cholinesterase properties. A coumarin, scoparone, was isolated from Platymiscium floribundum stems, and the flavonoids rutin and quercetin were isolated from Dimorphandra gardneriana beans. These compounds were purified using silica gel column chromatography, eluted with organic solvents in mixtures of increasing polarity, and identified by spectral analysis. In the leishmanicidal assays, the compounds showed dose-dependent efficacy against the extracellular promastigote forms, with an EC50 for scoporone of 21.4µg/mL, quercetin and rutin 26 and 30.3µg/mL, respectively. The flavonoids presented comparable results to the positive control drug, amphotericin B, against the amastigote forms with EC50 for quercetin and rutin of 10.6 and 43.3µg/mL, respectively. All compounds inhibited AChE with inhibition zones varying from 0.8 to 0.6, indicating a possible mechanism of action for leishmacicidal activity.

Nos últimos anos, o Ministério da Saúde do Brasil e a Organização Mundial da Saúde tem apoiado a investigação de novas tecnologias que possam contribuir para a vigilância, novos tratamentos e controle da leishmaniose visceral no país. Assim, o objetivo deste trabalho foi isolar compostos de plantas do bioma Caatinga, e investigar a toxicidade destes compostos contra as formas promastigotas e amastigotas de Leishmania infantum chagasi, principal parasita responsável pela leishmaniose visceral na América do Sul, e avaliar a sua capacidade para inibir a enzima acetil-colinesterase (AChE). Após a exposição aos compostos em estudo, foram realizados testes utilizando a forma promastigota que expressa luciferase e ELISA in situ para medir a viabilidade das formas promastigotas e amastigota, respectivamente. O ensaio colorimétrico MTT foi realizado para determinar a toxicidade destas substâncias utilizando células monocíticas murina RAW 264.7. Todos os compostos foram testados in vitro para as sua propriedade anti-colinesterásica. Um cumarina, escoparona, foi isolada a partir de hastes de Platymiscium floribundum, e os flavonóides, rutina e quercetina, foram isolados a partir de grãos de Dimorphandra gardneriana. Estes compostos foram purificados, utilizando cromatografia em coluna gel eluída com solventes orgânicos em misturas de polaridade crescente, e identificados por análise espectral. Nos ensaios leishmanicidas, os compostos fenólicos mostraram eficácia contra as formas extracelulares promastigotas, com EC50 para escoporona de 21.4µg/mL e para quercetina e rutina 26 e 30.3µg/mL, respectivamente. Os flavonóides apresentaram resultados comparáveis à droga controle, a anfotericina B, contra as formas amastigotas com EC50 para quercetina e rutina de 10.6 e 43.3µg/mL, respectivamente. Os compostos inibiram a enzima AChE com halos de inibição variando de 0,8 a 0,6cm, indicando um possível mecanismo de ação para a atividade leishmanicida.

Effects of marmin, a compound isolated from Aegle marmelos Correa, on contraction of the guinea pig-isolated trachea

Marmin or 7-[6', 7'-dihydroxygeranyl-oxy] coumarin is a compound isolated from Aegle marmelos Correa. In the study, we examined the effects of marmin on the contraction of guinea pig-isolated trachea stimulated by several inducers, namely histamine, metacholine, compound 48/80. We also evaluated its action against contraction induced by extracellular or intracellular calcium ion. The possibility of marmin to potentiate the

elaxation effect of isoprenaline was also studied. Marmin added in the organ bath at 10 min prior to the agonist inhibited the contraction elicited by histamine and metacholine in a concentration-dependent manner. Moreover, marmin antagonized the histamine-induced contraction in competitive manner. Marmin mildly potentiated the relaxation effect of isoprenaline. In the study, marmin abrogated the contraction of tracheal smooth muscle induced by compound 48/80, an inducer of histamine release. Besides, marmin successfully inhibited CaCl[2-]-induced contraction in Ca[2+] -free Krebs solution. Marmin also inhibited two phases of contraction which were consecutively induced by metacholine and CaCl[2] in Ca[2+]-free Krebs solution. Based on the results we concluded that marmin could inhibit contraction of the guinea-pig tracheal smooth muscle, especially by interfering histamine receptor, inhibiting the histamine release from mast, inhibiting intracellular Ca[2+] release from the intracellular store and the Ca[2+] influx through voltage-dependent Ca[2+] channels

Trypanocidal constituents in plants: 7. Mammea-type coumarins

Calophyllum brasiliense and Mammea americana (Clusiaceae) are two trees from the tropical rain forests of the American continent. A previous screening showed high trypanocidal activity in the extracts of these species. Several mammea-type coumarins, triterpenoids and biflavonoids were isolated from the leaves of C. brasiliense. Mammea A/AA was obtained from the fruit peels of M. americana. These compounds were tested in vitro against epimastigotes and trypomastigotes of Trypanosoma cruzi, the etiologic agent of Chagas disease. The most potent compounds were mammea A/BA, A/BB, A/AA, A/BD and B/BA, with MC100 values in the range of 15 to 90 g/ml. Coumarins with a cyclized ,-dimethylallyl substituent on C-6, such as mammea B/BA, cyclo F + B/BB cyclo F, and isomammeigin, showed MC100 values > 200 g/ml. Several active coumarins were also tested against normal human lymphocytes in vitro, which showed that mammea A/AA and A/BA were not toxic. Other compounds from C. brasiliense, such as the triterpenoids, friedelin, canophyllol, the biflavonoid amentoflavone, and protocatechuic and shikimic acids, were inactive against the epimastigotes. The isopropylidenedioxy derivative of shikimic acid was inactive, and its structure was confirmed by X-ray diffraction. Our results suggest that mammea-type coumarins could be a valuable source of trypanocidal compounds.

Phytochemical and some pharmacological properties of certain plants belonging to Asteraceae family

The aerial parts of three plants belonging to Family Asteraceae: Inula crithmoides, Iphiona scarab and Jasonia montana were investigated. Phytochemicals isolated from Inula crithmoides were identified as: isopimpinellin [I], scoparone [II], psoralene [III], kaempferol-3-O-alpha-L-rhamnopyranoside [IV], kaempferol -3, 7- di-O-alpha-L-rhamnopyranoside [V], kaempferol-3-O-beta- D-glucopyranoside-7-O-alpha-L-rhamnopyranoside [VI] and isorhamnetin-3-O-beta-D-glucopyranoside-7-O-alpha-L-rhamnopyranoside [VII]. From Iphiona scarba umbelliferone [VIII], xanthotoxol [IX], marmesin [X], alpha-amyrin [XI], stigmasterol [XII] and beta-sitosterol [XIII] were isolated. Moreover, Jasonia montana was found to contain 7-hydroxy-3, 5, 6, 3',. 4'-pentamethoxy flavone [XIV], 5, 7-dihydroxy- 3, 6, 3', 4' -tetramethoxy flavone [XV] and 5, 7-dihydroxy-3, 3', 4' -trimethoxy flavone [XVI], in addition to ferulic acid, caffeic acid, chrorogenic acid, alpha-amyrin, stigmasterol and beta-sitosterol. Inula crithmoides aqueous methanolic extract showed significant inhibitory effect on mouse lymphoma [Cell line L1210] in vitro study in concentration dependant manner starting from 12.5 up to 250 microg/ml [20 - 100% inhibition], respectively. In vivo study, the results indicated that Inula crithmoides methanolic extract had significant antioxidant effect against mycotoxin [Ochratoxin A]-induced oxidative stress in rat. Iphiona scabra and Jasonia montana ethanolic extracts showed potent acute anti-inflammatory, anticoagulant and hypotenssive activities comparing to the standard drugs [indomethacine]

Aurapten, a coumarin with growth inhibition against Leishmania major promastigotes

Several natural compounds have been identified for the treatment of leishmaniasis. Among them are some alkaloids, chalcones, lactones, tetralones, and saponins. The new compound reported here, 7-geranyloxycoumarin, called aurapten, belongs to the chemical class of the coumarins and has a molecular weight of 298.37. The compund was extracted from the Rutaceae species Esenbeckia febrifuga and was purified from a hexane extract starting from 407.7 g of dried leaves and followed by four silica gel chromatographic fractionation steps using different solvents as the mobile phase. The resulting compound (47 mg) of shows significant growth inhibition with an LD50 of 30 æM against the tropical parasite Leishmania major, which causes severe clinical manifestations in humans and is endemic in the tropical and subtropical regions. In the present study, we investigated the atomic structure of aurapten in order to determine the existence of common structural motifs that might be related to other coumarins and potentially to other identified inhibitors of Leishmania growth and viability. This compound has a comparable inhibitory activity of other isolated molecules. The aurapten is a planar molecule constituted of an aromatic system with electron delocalization. A hydrophobic side chain consisting of ten carbon atoms with two double bonds and negative density has been identified and may be relevant for further compound synthesis.

Esteróides e cumarina em calos de Mikania glomerata Sprengel / Steroides and coumarin from callus of Mikania Glomerata Sprengel

O estudo fitoquímico do extrato diclorometânico dos calos obtidos a partir de segmentos foliares de Mikania glomerata Sprengel resultou no isolamento dos esteróides campesterol, estigmasterol e ß-sitosterol e da cumarina, não tendo sido detectado nenhum diterpeno do tipo caurano

Chemical constituents of dichrostachys cinera, Haematoxylon campechianum and Sopher japonica leaves

The chemical constituents of Dicheostachys cinera, Hematoxylon campechianum and Sophora japonica leaves [Fam. Leguminosa] were studied. The coumarin fraction of D. cinera leaves was found to contain imperatorin I, marmesin II and esculetin III, whereas, stigmasterol IV and beta-sitosterol V were isolated from the unsaponifiable fraction. The coumarin fraction of H. campechianum leaves led to isolation of imperatorin I, umbelliferone VI and marmesin II, whereas, beta-amyrin VII, stigmasterol IV and beta-sitosterol V were isolated from the unsaponifiable fraction. Also, the coumarin fraction of S. japonica leaves was found to contain herniarin VIII, scopoletin IX, umbelliferone VI, marmesin II and esculetin III whereas, stigmasterol IV and beta-sitosterol V were isolated from the unsaponifiable fraction

Antimicrobial studies on fractions and pure compounds of caulophyllum inophllum Linn

An evergreen medicinal plant, Calophyllum inophyllum Linn. [Guttiferae], is cultivated as an ornamental plant through out Pakistan and medicinally used as antiseptic, astringent, expectorant, analgesic, diuretic and purgative. The chemical investigations revealed organic compounds viz. cholesterol, friedelin, canophyllol, canophyllic acid, inophynone, isoinophynone, 1,4, 5, 6 - tetrahydroxy - 2 - oxo - cycloheptene and biological studies [anti - bacterial and anti- fungal activities] of fractions [n - butanol, ethanol, chloroform and aqueous] and pure compounds [friedelin, canophyllol, canophyllic acid and inophynone] showed significant and non - significant results against Staphylococcus aureus, Streptococcus pyogenes, Corynebacterium diphtheriae, Bacillus subtilis [Gram + ve], Escherichia coli, Salmonella typhi, Shigella boydii, Klebsiella pneumonia, Proteus mirabilis, Pseudomonas aeroginosa [Gram - ve], Epidermophyton floccosum, Trichophyton rubrum, T. schoenleinii, Pseudallescheria boydii, Candida albicans, Aspergillus niger [human pathogens], Microsporum canis, Trichophyton simii, T. metagrophyton [animal pathogens], Fusarium oxysporum var. lycopersici, F. solani var. lycopersici, Macrophomina phaseolina [plant pathogens]

Coumarins with antiviral and cytotoxic activity from Egyptian panunculus asiaticus L

Three coumarins were isolated from the CHCl3 extract of the aerial parts of Ranunculus asiaticus L. [Ranunculaceae]. They were identified as aesculetin dimethyl ether [6,7-dimethoxy-coumarin] [I], isoscopoietin [II] and scopoietin [III], based on their spectral and physical data. The cytotoxic and antiviral activities of I and III were evaluated

chemical constituents of mandragora autumnalis

Seven alkaloids and five coumarins have been identified from the roots, leaves, unripe fruits and seeds of M and ragora autumnalis, which grows widely in Jordan. The isolated alkaloids were atropine, apoatropine, hyoscyamine, scopolamine, belladonine, cuscohygrine and scopine. The isolated coumarins are herniarin, umbelliferone, angelicin, scopoletin and scopolin. Sucrose and chlorogenic acid were also isolated and identified

Constituents of the aerial parts and roots of some solanum melanogen varieties

The aerial parts of Solanum melongena varieties Esculentum nees [Balady Black Long, Balady White Long and Round Black, Fam. Solanaceae] were exhaustively extracted with ethanol [90%] and fractionated into coumarin and unsaponifiable fractions. The coumarin fraction led to the isolation of bergapten [I], umbelliferone [II] and asculetin [III] whereas, beta-amyrin [IV], a mixture of steroidal component viz. stigmasterol [V], beta-sitosterol [VI] and campesterol [VII] were isolated from the unsaponifiable fraction of each plant material in different ratios and were identified using GLC. Also, the roots of Solanum melongena varieties were defatted and treated with ammonium hydroxide to afford the alkaloidal glycoside fractions which were found to contain solasonine [VIII] and solamargine [IX]. Acid hydrolysis of the glycoside mixture indicated the presence of solasodine [X] and a sapogenin diosgenin [XI]

Coumarins form the in-vitro culture of convolvulus arvensis L

Further investigation of the previously reported in vitro culture of Convolvulus arvensis L. revealed the presence of umbelliferone and scopolet in their identity was confirmed by co-chromatography with authentic samples and their UV data. The composition of the growth regulators, inclusion of yeast extract, sucrose content of the medium and induction of the culture greening by its illumination were found to have a prominent effect on the accumulation level of the coumarins. The greened callus was found to be unable to synthesize neither flavonoids nor alkaloids

Lipids and coumarins of astragalus trigones and rhynchosia minima

The aerial parts of both Astragalus trigonus DC. and Rhynchosia minima L. [Fam. Leguminosae] were exhaustively extracted with ethanol [90%] and fractionated into coumarin and unsaponifiable fractions. The coumarin fraction of A. trigonus was found to contain bergapten [I] and xanthotoxin [II], whereas waxy hydrocarbons, beta-amyrin [III] and beta-sitosterol [IV] were isolated from the unsaponifiable fraction. The coumarin fraction of R. minima was found to contain bergapten [I], isopimpinellin [V] and umbelliferone [VI], whereas waxy hydrocarbons and beta-sitosterol [IV] were isolated from the unsaponifiable fraction. Also, the fatty acids of both plants were studied by GLC of their methyl esters